rs10888838

Positions:

• chr1-54207424-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016491.4(MRPL37):​c.646+2014C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,096 control chromosomes in the GnomAD database, including 2,244 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2244 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL37 NM_016491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969

Genes affected

MRPL37 (HGNC:14034): (mitochondrial ribosomal protein L37) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL37	NM_016491.4	c.646+2014C>T		intron_variant		ENST00000360840.9	NP_057575.2
MRPL37	NM_001330602.1	c.646+2014C>T		intron_variant			NP_001317531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL37	ENST00000360840.9	c.646+2014C>T		intron_variant		1	NM_016491.4	ENSP00000354086	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23304 AN: 151976 Hom.: 2239 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.154

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.153 AC: 23317 AN: 152096 Hom.: 2244 Cov.: 32 AF XY: 0.160 AC XY: 11872 AN XY: 74340

Gnomad4 AFR AF: 0.0977

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.153

Alfa AF: 0.147 Hom.: 2340

Bravo AF: 0.152

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10888838; hg19: chr1-54673097;